Metal-Free Oxidative Amidation of 2-Oxoaldehydes: A Facile Access to α-Ketoamides

Abstract

A novel and efficient method for the synthesis of α-ketoamides, employing a dimethyl sulfoxide (DMSO)-promoted oxidative amidation reaction between 2-oxoaldehydes and amines under metal-free conditions is presented. Furthermore, mechanistic studies supported an iminium ion-based intermediate as a central feature of reaction wherein C1-oxygen atom of α-ketoamides is finally derived from DMSO.

SeO2 mediated efficient synthesis of amides and α-ketoamides of secondary amines with wide substrate scope

“…1 pharmaceuticals (rapamycin, enzyme inhibitors) and agrochemicals (FK506). 2-4 α-Ketoamides are synthesized from diverse substrates such as methyl-ketones, 5-10 aldehydes/arylglyox-als, [11][12][13][14][15][16] -ketoacids, [17][18][19][20] terminal alkynes, [21][22][23][24] cyanamides, 25 carbamoyl stannane/ silane with acid chlorides, [26][27][28] addition of aroyl to aryl-acetamides, 29 2,2-dibromo-1-aryl ethanones 30 and double carbonylation of aryl iodides. [31][32][33] Usually in these oxidative amidation, a co-oxidant is required.…”

KI‐I2‐DMSO: An Improved Microwave‐Assisted Selective Oxidation of Alkenes into 1,2‐Diketones

“…Since literature provides DMSO is most likely to be the true oxidant and the reaction in other solvents has not given the desired products in high yield; so the presence of DMSO is required to proceed the reaction. With KI and I 2 enhanced the reaction rate and forms the iodonium ion intermediate I , which undergoes ring opening with nucleophilic addition of the oxygen atom of DMSO and giving compound II , which is stabilized by DMSO itself ,. With the replacement of oxygen atom in next step forms intermediate III with HI as leaving group achieved the resulting 1,2‐diketones.…”

Aminocatalytic Cross‐Coupling Approach via Iminium Ions to Different CC Bonds

“…We initiated our studies by carrying out reactions of 50 mol % of pyrrolidine (2 a) and phenylglyoxal (1 a) with various nucleophiles, such as indoles 3, pyrroles 4, phenols 5, and b-naphthol (6) in DMSO under the conditions used in our earlier method [8] ( Table 1). Of the different nucleophiles tested, indole/N-substituted indoles 3 and pyrroles/N-substituted pyrroles 4 furnished C-3 cross-coupled products 8 and 9, respectively, in about 30 % yield.…”

“…Recently, we established a method based on iminium ions for the synthesis of a-ketoamides. [8] The potential of this method was demonstrated in the context of the direct amidation reaction between 2-oxoaldehydes (OAs) and secondary amines via iminium intermediate II under mild reaction conditions. However, although achieving this process by means of a DMSO-promoted oxidative amidation reaction is important, it could not be applied as a general method for amide-bond formation, particularly from iminium intermediate I, generated by reactions of aldehydes and secondary amines (Figure 1 a).…”